The aging lacrimal gland: Changes in structure and function

The afferent nerves of the cornea and conjunctiva, efferent nerves of the lacrimal gland, and the lacrimal gland are a functional unit that works cooperatively to produce the aqueous component of tears. A decrease in the lacrimal gland secretory function can lead to dry eye disease. Because aging is a risk factor for dry eye disease, study of the changes in the function of the lacrimal gland functional unit with age is important for developing treatments to prevent dry eye disease. No one mechanism is known to induce the changes that occur with aging, although multiple different mechanisms have been associated with aging. These fall into two theoretical categories: programmed theories of aging (immunological, genetic, apoptotic, and neuroendocrine) and error theories of aging (protein alteration, somatic mutation, etc). Lacrimal glands undergo structural and functional alteration with increasing age. In mouse models of aging, it has been shown that neural stimulation of protein secretion is an early target of aging, accompanied by an increase in mast cells and lipofuscin accumulation. Hyperglycemia and increased lymphocytic infiltration can contribute to this loss of function at older ages. These findings suggest that an increase in oxidative stress may play a role in the loss of lacrimal gland function with age. For the afferent and efferent neural components of the lacrimal gland functional unit, immune or inflammatory mediated decrease in nerve function could contribute to loss of lacrimal gland secretion with age. More research in this area is critically needed.

Age-dependent changes in rat lacrimal gland anti-oxidant and vesicular related protein expression profiles

Purpose: Anti-oxidation and exocytosis are important for maintaining exocrine tissue homeostasis. During aging, functional and structural alterations occur in the lacrimal gland (LG), including oxidative damage to proteins, lipids, and DNA. The aims of the present study were to determine in the aging LG: a) the effects of aging on LG structure and secretory activity and b) changes in the expression of oxidative stress markers. Methods: To address these goals, tear secretion composition and corneal impression cytology were compared between male Wistar rats of 2 (control) and 24 (aged) months. LG morphology and the expression levels of vitamin E and malonaldehyde (MDA) were evaluated to determine the anti-oxidant activity and lipid peroxidation, respectively. RT-PCR and western blot analysis were used for the analysis of Ras related in brain GTPase protein (Rab) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins of the secretory machinery (i.e.; Rab 3d, Rab 27, vesicle-associated membrane protein-2 (Vamp-2), and syntaxin). Results: Histological analysis of aged rats revealed a higher frequency of corneal epithelia metaplasia. In the acinar cells, organelles underwent degeneration, and lipofucsin-like material accumulated in the cytoplasm along with declines in the anti-oxidant marker vitamin E. Rab3d and Rab27b mRNA levels fell along with Rab3d protein expression, whereas syntaxin levels increased. Conclusions: These findings indicate that exocytotic and anti-oxidant mechanisms become impaired with age in the rat LG. In parallel with these structural alterations, functional declines may contribute to the pathophysiology caused by tear film modification in dry eye disease.

Influence of insulin treatment on the lacrimal gland and ocular surface of diabetic rats

Previous studies have observed changes in the lacrimal gland and ocular surface related to diabetes mellitus and related it to insulin resistance or insufficiency and oxidative damage. The aim of this study was to evaluate whether insulin treatment inhibits those changes. Diabetes was induced in male Wistar rats with a single intravenous injection of streptozotocin and a subgroup was treated with insulin. After 5 and 10 weeks, the three groups (n = 5-10/group/experimental procedure) were compared for biochemical, functional, and histological parameters. After 5 weeks, changes in morphology and increased numbers of lipofucsin-like inclusions were observed in lacrimal glands of diabetic but not insulin-treated rats. After 5 weeks, malonaldehyde and total peroxidase activity were significantly higher in diabetic rats, but similar to control in insulin-treated diabetic rats (P = 0.03, P = 0.02, respectively). Our data indicate that diabetes induces histological alterations in lacrimal gland and suggests that hyperglycemia-related oxidative stress may participate in diabetic dry eye syndrome. Prevention by insulin replacement suggests direct hormone action and/or benefit by early sub optimal metabolic control.

Aspirin prevents diabetic oxidative changes in rat lacrimal gland structure and function

The aim of this study is to evaluate whether aspirin reduces Diabetis Mellitus (DM) oxidative damage in the lacrimal gland (LG), and ocular surface (OS). Ten weeks after streptozotocin induced DM and aspirin treatment, LG and OS of rats were compared for tear secretion, hidtology, peroxidase activity, and expression of uncoupling proteins (UCPs). DM reduction of tear secretion was prevented by aspirin (P < 0.01). Alterations of LG morphology and increased numbers of lipofucsin-like inclusions were observed in diabetic but not in aspirin-treated diabetic rats. Peroxidase activity levels were higher and UCP-2 was reduced in DM LG but not in aspirin treated (P = 0.0025 and P < 0.05, respectively). The findings prevented by aspirin indicate a direct inhibitory effect on oxidative pathways in LG and their inflammatory consequences, preserving the LG structure and function against hyperglycemia and/or insulin deficiency damage.

Adenocarcinome au sein d'un adenome pleomorphe de la glande lacrymale. A propos d'un cas. [Adenocarcinoma in a pleomorphic adenoma of the lacrimal gland: a case study]

PURPOSE: To report a patient with an adenocarcinoma in a pleomorphic adenoma of the lacrimal gland. Adenocarcinoma constitutes a distinct group of epithelial malignancies of the lacrimal gland. METHODS: The clinical presentation, workup, surgical approach, and pathological findings were reviewed. RESULTS: A 56-year-old man presented with a 3-month history of a lacrimal fossa mass. This patient presented a painless mass in the upper outer eyelid with significant displacement of the globe. The tumor was localized to the lacrimal gland. Radiological investigations showed a round, well-defined lesion in the fossa of the lacrimal gland. We performed a lateral orbitotomy; en bloc resection was accomplished. The final specimen showed an adenocarcinoma in a pleomorphic adenoma. No recurrences were detected during follow-up. CONCLUSION: Although adenocarcinoma has rarely been reported in association with a pleomorphic adenoma of the lacrimal gland, this combination can exist. If the malignant tumor is limited in the pleomorphic adenoma, the prognosis appears to be better than in cases of local extension. Adjuvant therapy, radiation or others, are not useful.

Anatomical aspects of the lacrimal gland of the tufted capuchin (Cebus apella)

In the tufted capuchin (Cebus apella) the main lacrimal gland is composed of 2 distinct portions with an intraorbital and extraorbital localisation, interconnected by a bridge of glandular tissue which crosses the lateral orbital wall through the lateral orbital fissure located in the sphenozygomatic suture. The intraorbital lacrimal gland is flattened and extremely thin, with a variable outline. It lies on the upper and outer third of the globe of the eye, and the aponeurosis and the belly of the lateral rectus muscle, extending antero-posteriorly from the upper lateral angle of the orbit midway along the orbital cavity. The extraorbital lacrimal gland is compact, halfmoon-shaped, with 3 surfaces, 3 borders and 2 extremities. It lies in the temporal fossa between the temporalis muscle and the temporal surface of the zygomatic bone, fitting into a depression in this bone, and totally surrounded by adipose tissue. The secretory cells have a flocculent appearance and either low or high density. They possess a basal region containing the nucleus and rich in granular endoplasmic reticulum, and an apical region filled with secretory granules varying in size, form and density.

Prevention of radiochemotherapy-induced toxicity with amifostine in patients with malignant orbital tumors involving the lacrimal gland: a pilot study

BACKGROUND: To use amifostine concurrently with radiochemotherapy (CT-RT) or radiotherapy (RT) alone in order to prevent dry eye syndrome in patients with malignancies located in the fronto-orbital region. METHODS: Five patients (2 males, 3 females) with diagnosed malignancies (Non-Hodgkin B-cell Lymphoma, neuroendocrine carcinoma) involving the lacrimal gland, in which either combined CT-RT or local RT were indicated, were prophylactically treated with amifostine (500 mg sc). Single RT fraction dose, total dose and treatment duration were individually adjusted to the patient's need. Acute and late adverse effects were recorded using the RTOG score. Subjective and objective dry eye assessment was performed for the post-treatment control of lacrimal gland function. RESULTS: All patients have completed CT-RT or RT as indicated. The median total duration of RT was 29 days (range, 23 - 39 days) and the median total RT dose was 40 Gy (range, 36 - 60 Gy). Median lacrimal gland exposure was 35.9 Gy (range, 16.8 - 42.6 Gy). Very good partial or complete tumor remission was achieved in all patients. The treatment was well tolerated without major toxic reactions. Post-treatment control did not reveal in any patient either subjective or objective signs of a dry eye syndrome. CONCLUSION: The addition of amifostine to RT/CT-RT of patients with tumors localized in orbital region was found to be associated with absence of dry eye syndrome.

Afecções oculares em crianças de 2 a 8 anos da rede pública municipal de Piracicaba - SP

Study model: observacional, retrospective. Objective: to determine the frequence of the ametropic errors and other ocular problems in children with 2 to 8 year-old at Piracicaba - SP. Patients and Method: During the school year of 2000, 1001 children enrolled at the public schools of Piracicaba - SP, age ranged from 2 to 8 years old, were referred to complete ophthalmological exam. Visual acuity was previously determined using Snellen chart, applied by school teachers. Those children presenting visual acuity equal or less than 0.8, visual complaints or visual disorders were selected to appointment. Results: 51 children (5.09%) did not attended to examination. 950 children were submitted to complete ophthalmological exam. Ametropic errors were found 70.84% of the children. The most prevalent refractive errors were Hypermetropic Astigmatism (49.62%) and Hypermetropia (32,98%). Anisometropia was found in 1.78% children. Other ocular disabilities accounted for 10.21% of the examined children, such as strabismus (3.36%), eyelid changes, allergic conjunctivitis, congenital dacryostenosis, optic atrophy, corioretinitis and congenital glaucoma. Conclusion: The frequence of ocular problems observed let us to conclude the screening programs are valid surveys on decreasing rates of preventable blindness in our country.

The Role of Dyslipidemia on Ocular Surface, Lacrimal and Meibomian Gland Structure and Function

Purpose: Dyslipidemia is characterized by high lipid blood levels that are risk factors for cardiovascular diseases, which are leading causes of death. However, it is unclear whether dyslipidemia is a cause of the dry eye syndrome (DES). Therefore we determined in transgenic mice models of dyslipidemia, whether there is an association with DES development. Methods: Dyslipidemic models included male and female adult mice overexpressing apolipoprotein CIII (Apo CIII), LDL receptor knockout (LDLR-KO) and ApoE knockout (ApoE-KO). They were compared with age-and gender-matched C57BL/6 mice. Ocular health was evaluated based on corneal slit lamp assessment, phenol red thread test (PRT) and impression cytology. Blood lipid profiles and histology of meibomian and lacrimal glands were also evaluated. Effects of high-fat diet and aging were observed in LDLR-KO and ApoCIII strains, respectively. Results: Body weight and lacrimal gland weight were significantly higher in male mice compared to females of the same strain (P < 0.05). Body weight was significantly lower in LDLRKO mice receiving high lipid diet compared to their controls (P = 0.0043). ApoE-KO were hypercholesterolemic and ApoCIII hypertriglyceridemic while LDLR-KO showed increases in both parameters. The PRT test was lower in male LDLR-KO mice with high-fat diet than control mice with standard diet (P = 0.0273). Aging did not affect lacrimal structural or functional parameters of ApoCIII strain. Conclusions: DES development is not solely dependent on dyslipidemia in relevant mice models promoting this condition. On the other hand, lacrimal gland structure and function are differentially impacted by lipid profile changes in male and female mice. This dissociation suggests that other factors beside dyslipidemia impact on tear film dysfunction and DES development.

Les adénocarcinomes kystiques de la glande lacrymale [Cystic adenocarcinomas of the lacrymal gland]

Adenoid cystic carcinoma of the lacrimal gland. BACKGROUND: Adenoid cystic carcinoma is the most frequent epithelial tumour of the lacrimal gland. It represents 1.6 % of the orbital tumours. The aim of this study is to present a series of such patients who were followed up in our clinic and to discuss their clinical management in order to achieve a better life prognosis. MATERIALS AND METHODS: The cases we followed up in our department were presented, the treatment modalities were discussed, and conclusions were drawn. RESULTS: Six patients with this pathology were examined, 3 men and 3 women, aged 31 to 69 years. A large excision was performed in 5 patients (exenteration alone or extended exenteration with complementary radiotherapy) and in 1 patient with excision of the tumour followed by radiotherapy. One patient died due to carcinoma six years after the first surgery. The median follow-up period of our cases is 25 months. CONCLUSION: Adenoid cystic carcinoma of the lacrimal gland is a malignant tumour with a reserved prognosis. Various treatments were proposed to improve the mortality rate of the disease. At present radical surgery with or without complementary therapy seems to give the best chances of healing, at least with short or mid-term follow-up.

Histometry of the sublingual gland in male and female mice (Mus musculus) infected with the RAL strain of the Chagas parasite, Trypanosoma cruzi

Trypanosoma cruzi. The aim of this work was to analyze histologically and histometrically the sublingual gland of mice infected with the RAL strain of T cruzi, according to the sex. Swiss mice (Mus musculus) were inoculated with 2 x 10(4) blood trypomastigotes of the RAL strain of T cruzi. In the peak of the parasitemia (12th day) the mice were sacrificed, and the sublingual glands were fixed in ALFAC. HE-stained histological sections were evaluated histometrically. The parasitemia was higher in females. Histopatologically, acini of the infected animals were smaller, with scanty production of secretion, and smaller striated ducts. The nuclei of the demilunes were smaller and showed amastigote nests in the cytoplasm. Karyometrically, nuclei of the acini, demilunes and striated ducts were smaller in the infected mice. Stereologically, it was observed that relative volumes of acini and ducts were smaller and, inversely, relative volumen were greater for the conjunctive tissue in the infected males. The surface densities of acini and ducts were bigger and the diameter and thickness of the wall were smaller in this group. On the other hand, relative volume of acini was smaller and those of the ducts and conjunctive tissue were bigger in the infected females. The diameter and thickness of the wall of acini were smaller, and those of the striated ducts were bigger in this group. The RAL strain of T cruzi caused general atrophy in the sublingual gland, with numerous nests of parasites in the glandular parenchyma.

Submandibular gland aplasia and progressive dental caries: A case report

When severe caries occurs in mandibular permanent incisor teeth, the clinician should consider the possibility of associated submandibular gland aplasia or salivary hypofunction. Early diagnosis of submandibular gland disease is essential, as operative problems involving restoration of mandibular incisor teeth are considerable. Furthermore, progressive severe dental caries can present a dilemma for the clinician in affected individuals, despite intensive preventive and restorative therapy. A case report describing severe progressive dental caries and enamel demineralization of the permanent mandibular incisor teeth in a young girl is presented. Further investigation revealed absence of functional bilateral submandibular salivary glands contributing to the rapid breakdown of the teeth despite intensive preventive measures.

Different locations of dermoid cysts in the orbital region.

BACKGROUND: Dermoid cysts are frequent unilateral congenital benign tumors that can be found at different locations throughout the body. In the orbital region, dermoid cysts occur predominantly in the supero-temporal quadrant. However, different orbital locations are possible, making this entity an important differential diagnosis for orbital tumors. PATIENTS AND METHODS: We retrospectively reviewed the charts of 23 consecutive patients operated in our institution between 2005 and 2014 for orbital tumors that were diagnosed as congenital dermoid or epidermoid cysts. RESULTS: There were 21 dermoid and 2 epidermoid cysts. The median age at surgery time was 7 years (range 1-41). There were 15 females and 8 males. Eleven cysts were located supero-temporally (47.8%), seven supero-medially (30.4%), two temporally (8.7%), one at the frontal bone (4.4%) and two in the fossa of the lacrimal gland (8.7%). The mean cyst diameter was 13.1 mm±5.0 (SD). None had signs of malignant disease. No recurrence was observed after complete excision. CONCLUSION: Dermoid cysts of orbital region are mostly located in the supero-temporal quadrant. However, other orbital locations are possible and dermoid cysts must thus be considered in the differential diagnosis of any mass in the orbital region.

Third eyelid gland protrusion in dogs: an experimental model proposal

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